Evidence map›Paper›PMID 34588517›Full record

ArticleScientific reports2021

TNF induces glycolytic shift in fibroblast like synoviocytes via GLUT1 and HIF1A.

Kathrin Koedderitzsch, Ekaterina Zezina, Lingzi Li, Matthias Herrmann, Nadine Biesemann

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 61 citations in OpenAlex.

  1. Review
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  3. Enolase-1 and Inflammation.Biomolecules · 2026
    Review
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  14. Gut microbes · 2025
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Kathrin KoedderitzschSanofi Immunology and Inflammation Research Therapeutic Area, Type 1/17 Immunology Cluster, Industriepark Hoechst, 65926, Frankfurt am Main, Germany.
Ekaterina ZezinaSanofi Immunology and Inflammation Research Therapeutic Area, Type 1/17 Immunology Cluster, Industriepark Hoechst, 65926, Frankfurt am Main, Germany.
Lingzi LiSanofi Immunology and Inflammation Research Therapeutic Area, Type 1/17 Immunology Cluster, Industriepark Hoechst, 65926, Frankfurt am Main, Germany.
Matthias HerrmannSanofi Immunology and Inflammation Research Therapeutic Area, Type 1/17 Immunology Cluster, Industriepark Hoechst, 65926, Frankfurt am Main, Germany.
Nadine BiesemannSanofi Immunology and Inflammation Research Therapeutic Area, Type 1/17 Immunology Cluster, Industriepark Hoechst, 65926, Frankfurt am Main, Germany. nadine.biesemann@sanofi.com.
Sanofi (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

TNF is a central cytokine in the pathogenesis of rheumatoid arthritis (RA). Elevated level of TNF causes local inflammation that affects immune cells and fibroblast-like synoviocytes (FLS). Nowadays, only 20-30% of patients experience remission after the standard of care therapy-antibodies against TNF. Interestingly, responders show reduced levels of GLUT1 and GAPDH, highlighting a potential link to cellular metabolism. The aim of the study was to investigate whether TNF directly affects the metabolic phenotype of FLS. Real-time respirometry displayed TNF-induced upregulation of glycolysis along with a modest increase of oxidative phosphorylation in FLS from healthy donors. In addition, TNF stimulation enhanced HIF1A and GLUT1 expression. The upregulation of HIF1A and GLUT1 reflects their enriched level in FLS from RA patients (RA-FLS). The inhibition of TAK1, HIF1a and hexokinase deciphered the importance of TNF/TAK1/HIF1A/glycolysis signaling axis. To prove that inhibition of glycolysis reduced the pathogenic phenotype, we showed that 2-deoxyglucose, a hexokinase inhibitor, partially decreased secretion of RA biomarkers. In summary, we identified a direct role of TNF on glycolytic reprogramming of FLS and confirmed the potency of immunometabolism for RA. Further studies are needed to evaluate the therapeutic impact especially regarding non-responder data.

Indexed as

Arthritis, RheumatoidCells, CulturedGlucose Transporter Type 1HumansHypoxia-Inducible Factor 1, alpha SubunitSynoviocytesTumor Necrosis Factor-alphaGlucose Transporter Type 1HIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitSLC2A1 protein, humanTumor Necrosis Factor-alpha

Identifiers

PMID34588517
PMCPMC8481345
OpenAlexW3202798298

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.